Project 3: Genetic Variants and Tobacco Use in Chinese Adolescents The aim of the Genetic Variants and Tobacco Use in Chinese Adolescents project is to better understand the genetic contribution to smoking behavior. Results from the first four years of the USC TTURC indicate that individual disposition and cultural context have a potentially important moderator effect on prevention programs. In this project, we hypothesize that genetic factors responsible for dispositional attributes, such as hostility and depression, act to both influence an individual's smoking behavior and to moderate the effectiveness of tobacco control intervention and prevention trials. To this end, we will conduct a genetic epidemiologic study of genetic polymorphisms in key candidate genes within the serotonin and dopamine systems and their impact on tobacco use. In addition to known functional variants, we will genotype over 250 SNPs in 17 candidate genes in 2,661 students from an existing cohort from Wuhan, China. A combination of genomic technologies, including highthroughput SNP genotyping on fiber optic array, GeneScan, Taqman assay and DNA sequencing, will be used to comprehensively profile genetic variations in the candidate genes. We will investigate the relation of these polymorphisms to dispositional attributes, such as hostility and depression, and smoking and alcohol use outcomes. Additionally, we will examine important interaction effects of these polymorphisms combined with the effects from dispositional attributes and from a school-based intervention program. We will implement hierarchical modeling to include knowledge regarding the biological mechanism for the serotonin and dopamine systems and Bayes model averaging to comprehensively evaluate the set of risk factors that best represents the underlying complexity of smoking behavior within a multifaceted social context. The results of the proposed study should enhance our knowledge of genetic predisposition to smoking and allow us to create more effective prevention programs that are specifically tailored to the various subgroups identified in this work.